Sobrier M L, Dastot F, Duquesnoy P, Kandemir N, Yordam N, Goossens M, Amselem S
Laboratoire de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U91, Hôpital Henri Mondor, Créteil, France.
J Clin Endocrinol Metab. 1997 Feb;82(2):435-7. doi: 10.1210/jcem.82.2.3725.
The GH receptor (GHR) is a member of the cytokine receptor superfamily; GH binding protein is the solubilized extracellular domain of the GHR. Abnormalities in the GHR produce an autosomal recessive form of GH resistance, the Laron syndrome, characterized by growth failure and the clinical appearance of severe GH deficiency despite elevated circulating GH levels. In 13 unrelated patients with undetectable levels of GH binding protein, we characterized nine novel mutations in the GHR gene. These molecular defects comprise three nonsense mutations (Q65X, W80X, and W157X), one frameshift (36delC), two splice defects (G-->A at 70 + 1, C-->T at 723), and three missense mutations (C38S, S40L, and W50R) located in the extracellular domain of the receptor, and thus would be expected to interfere with GH binding activity. These results further confirm the broad heterogeneity of mutations underlying this rare GH resistance syndrome.
生长激素受体（GHR）是细胞因子受体超家族的成员；生长激素结合蛋白是GHR的可溶性细胞外结构域。GHR异常会导致常染色体隐性遗传形式的生长激素抵抗，即拉伦综合征，其特征为生长发育迟缓，尽管循环生长激素水平升高，但临床表现为严重的生长激素缺乏。在13名生长激素结合蛋白水平检测不到的非亲缘关系患者中，我们鉴定出了生长激素受体基因中的9种新突变。这些分子缺陷包括三个无义突变（Q65X、W80X和W157X）、一个移码突变（36delC）、两个剪接缺陷（70 + 1处G→A、723处C→T）以及三个错义突变（C38S、S40L和W50R），它们位于受体的细胞外结构域，因此预计会干扰生长激素的结合活性。这些结果进一步证实了这种罕见的生长激素抵抗综合征背后突变的广泛异质性。
